Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Allergy. 2010 Jul;65(7):865-74. doi: 10.1111/j.1398-9995.2009.02291.x. Epub 2009 Dec 21.
The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood.
Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender.
Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort.
This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.
叉头框蛋白 P3（FOXP3）基因位于 X 染色体上，编码一种转录因子，指导 T 细胞向调节表型发展。调节性 T 细胞可能抑制特应性的发展。我们评估了 FOXP3 单核苷酸多态性（SNP）是否与儿童期特应性的发展有关。
在参与过敏研究的 3062 名儿童（51%为男孩）中，对 FOXP3 的 7 个 SNP 进行了基因分型，该研究由三个荷兰出生队列（PIAMA、PREVASC 和 KOALA）组成。在 1、2、4 和 8 岁时，分析了 FOXP3 SNP 与总血清 IgE 和致敏（存在对鸡蛋、牛奶和室内过敏原，即屋尘螨、猫和/或狗过敏原的特异性血清 IgE）的关系。采用方差分析和逻辑回归进行分析，按性别分层。
我们最一致的发现是观察到对鸡蛋和室内过敏原的致敏作用。在女孩中，有 5 个 FOXP3 SNP（rs5906761、rs2294021、rs2294019、rs6609857 和 rs3761548）与 1 岁和 2 岁时对鸡蛋的致敏以及 2 岁时对室内过敏原的致敏显著相关（P<0.05），但在 4 岁和 8 岁时没有，这一发现横跨三个队列。在 PIAMA 队列中，rs5906761 和 rs2294021 与男孩食物过敏原致敏的缓解有关。
这是第一项在三个队列中表明 X 染色体 FOXP3 基因型可能导致女孩在幼儿期对鸡蛋和室内过敏原致敏的研究。此外，在男孩中仅存在与食物过敏原致敏缓解的关联。
